Properties of Poly (Lactic-co-Glycolic Acid) and Progress of Poly (Lactic-co-Glycolic Acid)-Based Biodegradable Materials in Biomedical Research

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TL;DR

This review summarizes the synthesis, physicochemical properties, and degradation of PLGA, a biodegradable polymer approved by the FDA and EMA. It highlights recent applications of PLGA-based drug delivery systems in tumor diseases, neurodegenerative diseases, pulmonary diseases, bone tissue engineering, ocular disease, diagnostics, immunomodulation, inflammatory diseases, cardiovascular diseases, and infections. The review concludes that PLGA-based systems improve drug bioavailability and reduce side effects, but challenges such as low drug-loading capacity and acidic degradation products remain.

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**Background:** Biodegradable polymers, particularly poly(lactic-co-glycolic acid) (PLGA), have gained significant attention in biomedical research due to their biocompatibility, non-toxicity, and designable degradation time. PLGA is a copolymer of lactic acid (LA) and glycolic acid (GA) that degrades in the body into LA and GA, which are metabolized into carbon dioxide and water. It is approved by the FDA and EMA for use as a drug carrier. This review aims to illustrate the progress of PLGA research in biomedical applications and identify shortcomings to guide future development.

**Methods:** The authors conducted a literature search using Web of Science, PubMed, and CAS SciFinder for English-language articles published between 1995 and 2022. Keywords included "Drug delivery," "PLGA," "Synthesis," "Biodegradable," and "Applications." Articles were selected based on significant research advances in biomedicine within the last five years, excluding non-medical applications and older publications. The review covers PLGA's physicochemical properties, synthesis, degradation, and applications in various biomedical fields.

**Key Results:** The review describes two classical synthesis methods for PLGA: ring-opening polymerization and direct polycondensation. A novel metabolic engineering approach using Escherichia coli to produce PLGA from carbohydrates was highlighted, which lowers production costs. PLGA's physicochemical properties, such as molecular weight (typically 5–40 kDa), glass transition temperature (45–55 °C), and degradation rate, are influenced by the LA:GA ratio; a 50:50 ratio degrades fastest. Degradation occurs via hydrolytic ester bond cleavage and autocatalytic degradation, producing an acidic microenvironment that may cause local inflammation.

Applications of PLGA-based systems are detailed across multiple conditions: - **Tumor diseases:** Polyethylene glycolic PLGA nanoparticles encapsulating adriamycin reduced cardiomyopathy. Verteporfin-loaded PLGA microparticles significantly inhibited glioblastoma multiforme tumor growth in mice. Quercetin-PLGA microparticles showed effective antitumor activity against MCF-7 breast cancer cells at 1.5–3 g/mL. - **Neurodegenerative diseases:** Curcumin-loaded PLGA nanoparticles improved oral absorption twofold in mice. Selegiline PLGA nanoparticles had a drug penetration rate of 77.56% (vs. 65% for pure selegiline) and a half-life of ~13.5 h, with higher brain concentrations in rats. - **Pulmonary diseases:** HSPB5-loaded porous PLGA microparticles protected the protein from neutralization and inhibited lung inflammation in COPD model mice. Surface-modified PLGA microparticles with Labrafil enhanced macrophage targeting for tuberculosis treatment. - **Bone tissue engineering:** Graphene-PLGA fibers showed superior mechanical properties. PLGA/hydroxyapatite 3D-printed scaffolds with quaternized chitosan grafting enhanced anti-infection and bone regeneration in rat and rabbit models. PLGA/tricalcium phosphate scaffolds loaded with salvianolic acid B promoted osteogenesis and angiogenesis for spinal fusion. - **Ocular disease:** Chitosan-coated PLGA nanoparticles encapsulating triamcinolone acetonide achieved sustained release after 27 h. Dasatinib-loaded PLGA microparticles (>1.0 μm) showed sustained release for 55 days and reduced collagen matrix contraction. PLGA-PEG-POD nanoparticles improved ocular bioavailability. - **Diagnostics:** pH-sensitive PLGA nanoparticles encapsulating manganese oxide showed up to 35-fold MRI contrast variation in acidic environments. PLGA-iron oxide particles enabled photoacoustic tomography and MRI dual-modality tracking of tendon stem cells. - **Immunomodulation:** TGF-β1-loaded PLGA microparticles co-transplanted with mouse islets in diabetic mice showed long-term graft function with localized immune regulation. - **Inflammatory diseases:** Naringin-PLGA nanoparticles at 20 mg/kg reduced rheumatoid factor and C-reactive protein levels in arthritis mouse models. Licochalcone-A-loaded PLGA nanoparticles with cell-penetrating peptide B6 showed stronger anti-inflammatory effects. - **Cardiovascular diseases:** A PLGA-VLP implant vaccine targeting S100A9 reduced serum calcineurin, IL-1β, IL-6, and MCP-1 in atherosclerosis models. t-PA-PEG-PLGA nanoparticles showed 2–6 times higher thrombolytic activity than free t-PA. - **Infection:** Red blood cell membrane-coated PLGA nanoparticles loaded with tedizolid phosphate (192.50 ± 5.85 nm) reduced phagocytosis and neutralized MRSA exotoxin. PLGA film-forming systems loaded with terbinafine hydrochloride were developed for superficial fungal infections.

**Clinical Implications:** PLGA-based drug delivery systems offer significant advantages, including improved drug bioavailability, reduced side effects, and sustained release, which can enhance patient compliance. However, challenges remain, such as low drug-loading capacity, high production costs, difficulties in large-scale production, and the acidic degradation microenvironment that may cause local inflammation. The review emphasizes the need for further research on PLGA-drug interactions, quality control of PLGA derivatives, and translation of basic research into clinical applications. Despite these gaps, PLGA's FDA and EMA approval positions it as a promising material for future biomedical therapies.